Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion
Abstract
The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE; National Science Foundation (NSF); National Institutes of Health (NIH)
- OSTI Identifier:
- 1337193
- Resource Type:
- Journal Article
- Journal Name:
- Nucleic Acids Research
- Additional Journal Information:
- Journal Volume: 41; Journal Issue: 17; Journal ID: ISSN 0305-1048
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Chen, Y., Zhang, X., Dantas Machado, A. C., Ding, Y., Chen, Z., Qin, P. Z., Rohs, R., and Chen, L. Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion. United States: N. p., 2013.
Web. doi:10.1093/nar/gkt584.
Chen, Y., Zhang, X., Dantas Machado, A. C., Ding, Y., Chen, Z., Qin, P. Z., Rohs, R., & Chen, L. Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion. United States. https://doi.org/10.1093/nar/gkt584
Chen, Y., Zhang, X., Dantas Machado, A. C., Ding, Y., Chen, Z., Qin, P. Z., Rohs, R., and Chen, L. 2013.
"Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion". United States. https://doi.org/10.1093/nar/gkt584.
@article{osti_1337193,
title = {Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion},
author = {Chen, Y. and Zhang, X. and Dantas Machado, A. C. and Ding, Y. and Chen, Z. and Qin, P. Z. and Rohs, R. and Chen, L.},
abstractNote = {The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.},
doi = {10.1093/nar/gkt584},
url = {https://www.osti.gov/biblio/1337193},
journal = {Nucleic Acids Research},
issn = {0305-1048},
number = 17,
volume = 41,
place = {United States},
year = {Mon Jul 08 00:00:00 EDT 2013},
month = {Mon Jul 08 00:00:00 EDT 2013}
}